In vitro human skin absorption of linalool: Effects of vehicle composition, evaporation and occlusion on permeation and distribution.

In vitro human skin permeation and distribution of the fragrance material linalool (3,7-dimethyl-1,6-octadien-3-ol, CAS No. 78-70-6) following application in a range of single and mixed vehicles was determined, under unoccluded and occluded conditions, using human epidermal membranes. Vehicles were (70/30 v/v) ethanol[EtOH]/water, dipropyleneglycol [DPG], diethyl phthalate [DEP], (25/75 v/v) EtOH/DEP, (25/75 v/v) EtOH/DPG and petrolatum. Worst case absorbed dose values (% applied dose) for linalool under unoccluded conditions varied from 1.84% (DPG) to 4.08% (EtOH/water) and under occluded conditions from 5.9% (DEP) to 14.7% (EtOH/water). Occlusion always increased absorption but the magnitude of the effect varied with the vehicle from 2 to 6-fold. This study demonstrated that in vitro human skin permeation of linalool varied quite widely between test vehicles and that the magnitude of the effect of occlusion was also vehicle dependent. This was particularly significant in view of the reported variations in biological responses using different vehicles (Lalko et al., 2004; Politano et al., 2006).

Development of a pulsed, variable-energy positron beam for atomic scale defect studies.

Positron annihilation spectroscopy provides a sensitive means of non-destructive characterization of materials, capable of probing single atom vacancies in solids with 10-7 sensitivity. We detail here the development of a magnetically guided, variable energy, pulsed positron beam designed to conduct depth-dependent defect studies in metals, semiconductors, and dielectrics, which will be the first of its kind in the United States. The design of the target stage provides capabilities for measurements during in situ annealing up to 800 °C and incorporates a new approach to minimize the background due to energetic backscattered positrons. The developed beam at Bowling Green State University provides a powerful tool for characterization of thin films, devices, and ion irradiated materials.

A resistive-anode based position-sensitive Rydberg atom detector.

We describe here the development and characterization of a position-sensitive detector for Rydberg atom experiments. The detector builds on an earlier design that field-ionized incident Rydberg positronium (Ps) atoms and then electrostatically focused the freed positrons onto a micro-channel plate (MCP) detector without the use of a position sensitive anode. In this design, pulses from the MCP are deposited onto a resistive anode, providing a means of measuring the incident particles' x, y positions. The first detector constructed utilized a pair of MCPs in a chevron configuration and was used to observe the focusing of Rydberg Ps atoms from an electrostatic mirror. A second detector, developed for use in a measurement of the 1S-2S interval of Ps, incorporates three MCPs in a Z-stack configuration to produce larger pulses. Using a UV-induced signal, we have characterized the performance of the assembled detectors, finding a spatial resolution of ∼1.4 mm for the largest induced pulses and for pulse widths of ∼7-10 ns FWHM; pulse times can be resolved to better than 1 ns. The Ps induced signal is anticipated to yield pulses ∼5 times larger, which are expected to achieve a spatial resolution of <1 mm. Appropriate lenses could make possible applications involving either imaging a large area or magnifying a small area of the incident Ps spatial distribution.

Using Statistical Shape and Appearance Modelling to characterise the 3D shape and material properties of human lumbar vertebrae: A proof of concept study.

Patient variation affects the outcomes of a range of spinal interventions, from disc replacement to vertebral fixation and vertebroplasty. Statistical Shape and Appearance Modelling (SSAM) can be used to describe anatomical variation and pathological differences within the population. To better understand how bone density and shape variation affect load transfer with respect to surgical treatments, Finite Element (FE) models can be generated from a SSAM. The aim for this study is to understand whether geometric and density variation as well as multiple vertebral levels can be incorporated into a single SSAM and whether this can be used to investigate the relationships between, and effects of, the various modes of variation. FE models of 14 human lumbar vertebrae that had been µCT imaged and validated through experimental testing were used as input specimens for a SSAM. The validity of the SSAM was evaluated by using principal component analysis to identify the primary modes of geometric and bone density variation and comparing to those in the input set. FE models were generated from the SSAM to examine the response to loading. The mean error between the input set and generated models for volume, mean density and FE compressive stiffness were 10%, 3% and 10% respectively. Principal Component (PC) 1 captured the majority of the bone density variation. The remaining PCs described specific geometric variation. The FE models generated from the SSAM showed the variations in vertebral stiffness as a result of complex relationships between bone density and shape. The SSAM created has limited data for its input set, however, it acts as a proof of concept for the novel combination of material and shape variation into a single shape model. This approach and the tools developed can be applied to wider patient groups and treatment scenarios to improve patient stratification and to optimise treatments.

Emotion production of facial expressions: A comparison of deaf and hearing children.

The production of facial expressions is an important skill that allows children to share and adapt emotions during social interactions. While deaf children are reported to show delays in their social and emotion understanding, the way in which they produce facial expressions of emotions has been relatively unexplored. The present study investigated the production of facial expressions of emotions by young congenitally deaf children. Six facial expressions of emotions produced by 5 congenitally deaf children and 5 hearing children (control group) were filmed across three tasks: 1) voluntarily posed expression of emotion 2) responding to social stories 3) intentionally mimicking expressions of emotion. The recorded videos were analysed using a software based of the Facial Action Coding System (FACS), and then judged by adult raters using two different scales: according to the emotion elicited (i.e. accuracy) and the intensity of the emotion produced. The results of both measurement scales showed that all children (deaf and hearing) were able to produce socially recognisable prototypical configuration of facial expressions. However, the deaf children were rated by adults as expressing their emotions with greater intensity compared to the hearing children. The results suggest deaf children may show more exaggerated facial expressions of emotion, possibly to avoid any ambiguity in communication.

A new mechanism for void-cascade interaction from nondestructive depth-resolved atomic-scale measurements of ion irradiation-induced defects in Fe.

The nondestructive investigation of single vacancies and vacancy clusters in ion-irradiated samples requires a depth-resolved probe with atomic sensitivity to defects. The recent development of short-pulsed positron beams provides such a probe. Here, we combine depth-resolved Doppler broadening and positron annihilation lifetime spectroscopies to identify vacancy clusters in ion-irradiated Fe and measure their density as a function of depth. Despite large concentrations of dislocations and voids in the pristine samples, positron annihilation measurements uncovered the structure of vacancy clusters and the change in their size and density with irradiation dose. When combined with transmission electron microscopy measurements, the study demonstrates an association between the increase in the density of small vacancy clusters with irradiation and a remarkable reduction in the size of large voids. This, previously unknown, mechanism for the interaction of cascade damage with voids in ion-irradiated materials is a consequence of the high porosity of the initial microstructure.

Detector for positronium temperature measurements by two-photon angular correlation.

We report on the design and characterization of a modular γ-ray detector assembly developed for accurate and efficient detection of coincident 511 keV back-to-back γ-rays following electron-positron annihilation. Each modular detector consists of 16 narrow lutetium yttrium oxyorthosilicate scintillators coupled to a multi-anode Hamamatsu H12700B photomultiplier tube. We discuss the operation and optimization of 511 keV γ-ray detection resulting from testing various scintillators and detector arrangements concluding with an estimate of the coincident 511 keV detection efficiency for the intended experiment and a preliminary test representing one-quarter of the completed array.

Focusing of a Rydberg Positronium Beam with an Ellipsoidal Electrostatic Mirror.

Slow atoms in Rydberg states can exhibit specular reflection from a cylindrical surface upon which an azimuthally periodic potential is imposed. We have constructed a concave mirror of this type, in the shape of a truncated oblate ellipsoid of revolution, which has a focal length of (1.50±0.01) m measured optically. When placed near the center of a long vacuum pipe, this structure brings a beam of n=32 positronium (Ps) atoms to a focus on a position sensitive detector at a distance of (6.03±0.03) m from the Ps source. The intensity at the focus implies an overall reflection efficiency of ∼30%. The focal spot diameter (32±1) mm full width at half maximum is independent of the atoms' flight times from 20 to 60 µs, thus indicating that the mirror is achromatic to a good approximation. Mirrors based on this principle would be of use in a variety of experiments, allowing for improved collection efficiency and tailored transport or imaging of beams of slow Rydberg atoms and molecules.

Protection against maternal infection-associated fetal growth restriction: proof-of-concept with a microbial-derived immunomodulator.

Infection-associated inflammatory stress during pregnancy is the most common cause of fetal growth restriction and/or miscarriage. Treatment strategies for protection of at-risk mothers are limited to a narrow range of vaccines, which do not cover the bulk of the common pathogens most frequently encountered. Using mouse models, we demonstrate that oral treatment during pregnancy with a microbial-derived immunomodulator (OM85), currently used clinically for attenuation of infection-associated airway inflammatory symptoms in infants-adults, markedly reduces risk for fetal loss/growth restriction resulting from maternal challenge with bacterial lipopolysaccharide or influenza. Focusing on LPS exposure, we demonstrate that the key molecular indices of maternal inflammatory stress, notably high levels of RANTES, MIP-1α, CCL2, KC, and G-CSF (granulocyte colony-stimulating factor) in gestational tissues/serum, are abrogated by OM85 pretreatment. Systems-level analyses conducted in parallel using RNASeq revealed that OM85 pretreatment selectively tunes LPS-induced activation in maternal gestational tissues for attenuated expression of TNF, IL1, and IFNG-driven proinflammatory networks, without constraining Type1-IFN-associated networks central to first-line antimicrobial defense. This study suggests that broad-spectrum protection-of-pregnancy against infection-associated inflammatory stress, without compromising capacity for efficient pathogen eradication, represents an achievable therapeutic goal.

Large-area field-ionization detector for the study of Rydberg atoms.

We describe here the development and characterization of a micro-channel plate (MCP) based detector designed for the efficient collection and detection of Rydberg positronium (Ps) atoms for use in a time-of-flight apparatus. The designed detector collects Rydberg atoms over a large area (∼4 times greater than the active area of the MCP), ionizing incident atoms and then collecting and focusing the freed positrons onto the MCP. Here we discuss the function, design, and optimization of the device. The detector has an efficiency for Rydberg Ps that is two times larger than that of the γ-ray scintillation detector based scheme it has been designed to replace, with half the background signal. In principle, detectors of the type described here could be readily employed for the detection of any Rydberg atom species, provided a sufficient field can be applied to achieve an ionization rate of ≥108/s. In such cases, the best time resolution would be achieved by collecting ionized electrons rather than the positive ions.

Angle-Resolved Spectroscopy of Positronium Emission from a Cu(110) Surface.

The affinity A_{Ps} of positronium (Ps) atoms for a metal is the negative of the maximum kinetic energy with which Ps is emitted into vacuum when thermalized positrons in a metal encounter the surface. When this quantity is measured by ground state Ps time of flight (TOF), the precision is severely limited by the short triplet state lifetime of 142 ns. By quickly converting the emitted Ps atoms into long-lived Rydberg states, we are able to dramatically increase the TOF to allow precision measurements of A_{Ps}. From our measurements made on a Cu(110) sample at T=128 K, we find A_{Ps}(128 K)=(-2.476±0.010_{stat}±0.013_{syst}) eV, compared with the result A_{Ps}(128 K)=(-2.545±0.010_{num}±0.010_{syst}) eV found using highly accurate generalized gradient approximations for both electrons and positrons within density functional theory. Such precision opens up opportunities in the quest for an improved density functional.

Narrative skills in deaf children who use spoken English: Dissociations between macro and microstructural devices.

Previous research has highlighted that deaf children acquiring spoken English have difficulties in narrative development relative to their hearing peers both in terms of macro-structure and with micro-structural devices. The majority of previous research focused on narrative tasks designed for hearing children that depend on good receptive language skills. The current study compared narratives of 6 to 11-year-old deaf children who use spoken English (N=59) with matched for age and non-verbal intelligence hearing peers. To examine the role of general language abilities, single word vocabulary was also assessed. Narratives were elicited by the retelling of a story presented non-verbally in video format. Results showed that deaf and hearing children had equivalent macro-structure skills, but the deaf group showed poorer performance on micro-structural components. Furthermore, the deaf group gave less detailed responses to inferencing probe questions indicating poorer understanding of the story's underlying message. For deaf children, micro-level devices most strongly correlated with the vocabulary measure. These findings suggest that deaf children, despite spoken language delays, are able to convey the main elements of content and structure in narrative but have greater difficulty in using grammatical devices more dependent on finer linguistic and pragmatic skills.

Cortical Flow-Driven Shapes of Nonadherent Cells.

Nonadherent polarized cells have been observed to have a pearlike, elongated shape. Using a minimal model that describes the cell cortex as a thin layer of contractile active gel, we show that the anisotropy of active stresses, controlled by cortical viscosity and filament ordering, can account for this morphology. The predicted shapes can be determined from the flow pattern only; they prove to be independent of the mechanism at the origin of the cortical flow, and are only weakly sensitive to the cytoplasmic rheology. In the case of actin flows resulting from a contractile instability, we propose a phase diagram of three-dimensional cell shapes that encompasses nonpolarized spherical, elongated, as well as oblate shapes, all of which have been observed in experiment.

Monoenergetic positronium emission from metal-organic framework crystals.

Recently it has been discovered that positronium (Ps), after forming in metal-organic framework (MOF) crystals, is emitted into vacuum with a high efficiency and low energy that can only be explained by its propagating as delocalized Bloch states. We show that the Ps atoms are emitted from MOFs in a series of narrow energy peaks consistent with Ps at Bloch-state energy minima being emitted adiabatically into the vacuum. This implies that the Ps emission energy spectra can be directly compared with calculations to obtain detailed information about the Ps band structure in the MOF crystal. The narrow energy width of the lowest energy Ps peak from one MOF sample (2-Methylimidazole zinc salt ZIF-8) suggests it originates from a polaronic Ps surface state. Other peaks can be assigned to Ps with an effective mass of about twice that of bare Ps. Given the immense catalog of available MOF crystals, it should be possible to tune the Ps properties to make vastly improved sources with high production efficiency and a narrow energy spread, for use in fundamental physics experiments.

Spontaneously arising concurrent ileocaecal adenocarcinoma and renal pelvis transitional cell carcinoma in a rhesus macaque (Macaca mulatta).

A 25-year-old, female rhesus macaque (Macaca mulatta) presented with a history of weight loss despite a normal appetite and supportive care. The animal was humanely destroyed due to poor prognosis. Post-mortem examination revealed a focally extensive, firm, white annular constriction at the ileocaecal junction and an incidental finding of a pale white nodule approximately 0.8 cm in diameter in the left renal pelvis. Based on the microscopical findings, ileocaecal adenocarcinoma and renal pelvis transitional cell carcinoma (TCC) were diagnosed. The use of cytokeratin (CK)-7 and -20 and uroplakin III as potential renal TCC markers was evaluated. The neoplastic cells were labelled intensely with antibodies to uroplakin III, but not to CK-7 or -20. Spontaneous intestinal adenocarcinoma has been documented in the rhesus macaque, but concurrent renal pelvis TCC is highly unusual.

Role of vibrational dynamics in resonant positron annihilation on molecules.

Vibrational Feshbach resonances are dominant features of positron annihilation for incident positron energies in the range of the molecular vibrations. Studies in relatively small molecules are described that elucidate the role of intramolecular vibrational energy redistribution into near-resonant multimode states, and the subsequent coupling of these modes to the positron continuum, in suppressing or enhancing these resonances. The implications for annihilation in other molecular species, and the necessary ingredients of a more complete theory of resonant positron annihilation, are discussed.

Comparisons of positron and electron binding to molecules.

Positron binding to molecules is compared to the analogous electron-molecule bound states. For both, the bound lepton density is diffuse and remains outside the valence shell. Positron binding energies are found to be one to two orders of magnitude larger than those of the negative ions due to two effects: the orientation of the molecular dipole moment allows the positron to approach it more closely and, for positrons, lepton correlations (e.g., via dipole polarizability) contribute more strongly.

Self-similar curling of a naturally curved elastica.

We consider the curling of an initially flat but naturally curved elastica on a hard, nonadhesive surface. Combining theory, simulations, and experiments, we find novel behavior, including a constant front velocity and a self-similar shape of the curl that scales in size as t(1/3) at long times after the release of one end of the elastica. The front velocity is selected by matching the self-similar solution with a roll of nearly constant curvature located near the free end.